Field of the Invention
The inventions disclosed and taught herein relate generally to contrast agents and contrast agent markers for use in magnetic resonance imaging applications. More specifically, the inventions disclosed herein are related to novel contrast agents for use in MRI and related therapeutic imaging applications, as well as their manufacture and use in therapeutic devices and applications.
Description of the Related Art
Magnetic resonance imaging (“MRI”) is a powerful imaging modality having a number of applications, ranging from molecular diagnostics, imaging, and therapeutics. For example, molecular magnetic resonance imaging (MRI) offers the potential to image some events at the cellular and subcellular level and many significant advances have recently been witnessed in this field. The introduction of targeted MR contrast agents has enabled the imaging of sparsely expressed biological targets in vivo.
While MRI is perhaps best known as the optimal imaging modality for the prostate and surrounding critical organ structures, it's application, and the application of the contrast agents necessary in order to effectively track and utilize this and related techniques, are not limited to cancer therapy. For example, MRI imaging, and its related imaging modalities, are being used in a variety of applications, including therapeutic applications (both treatment and monitoring), in angiography applications, for monitoring patient intravascular blood flow, in following drug delivery, and for in vivo MRI tracking techniques, such as the tracking of mesenchymal stem cells in peripheral nerve injuries using paramagnetic contrast agents.
Even though the intrinsic magnetic resonance imaging (MRI) contrast is much more flexible than in other clinical imaging techniques, the diagnosis of several pathologies requires the involvement of contrast agents (CAs) that can enhance the difference between normal and diseased tissues by modifying their intrinsic parameters. Imaging modalities which also require the use of contrast agents to be most effective in their therapeutic applications include in vivo near-infrared fluorescence (NIRF) imaging, magnetic resonance imaging (MRI), positron emission tomography (PET), computed tomography (CT), ultrasound (US), and photoacoustic imaging (PAI). In general, clinical and preclinical applications of contrast agents, particularly indirect contrast agents, have been identified for a broad spectrum of imaging applications. MRI CAs and related contrast agents are indirect agents because they do not become visible by themselves as opposed to other imaging modalities.
Nanoparticle-based contrast agents are also a developing approach, and are quickly becoming valuable and potentially transformative tools for enhancing medical diagnostics for a wide range of in vivo imaging modalities. Compared with conventional molecular-scale contrast agents, nanoparticles (NPs) promise improved abilities for in vivo detection and potentially enhanced targeting efficiencies through longer engineered circulation times, designed clearance pathways, and multimeric binding capacities.
MRI-CT fusion has been shown to improve postimplant quality assessment over CT alone, but this combined imaging approach has not been translatable to the community setting owing to inadequacies of fusing caused by imaging with different bladder and rectal filling, prostate volumetric differences between imaging modalities, and difficulties fusing the negative contrast of the seeds, strands of seeds, and needle tracks with the seeds visualized on CT scan. See, Crook, J., et al., “Interobserver Variation Inpostimplant Computed Tomography Contouring Affects Quality Assessment of Prostate Brachy therapy,” Brachytherapy, 2002, Vol. 1(2), pp. 66-73 (2002).
The consequence of the current inadequate ultrasound and CT imaging is subjective dosimetric evaluation and poor quality assurance during and after brachytherapy. Poor-quality implants are of critical clinical importance because they lead to decreased cure rates and increased side effects after treatment. Therefore, there is a critical need for national standardization of prostate brachytherapy dosimetry. This effort may be achieved through the design of seed implants of improved design that incorporate high contrast imaging capabilities.
The inventions disclosed and taught herein are directed to new and improved contrast and imaging agents for use in a variety of medical imaging modalities, as well as seeds and strands containing such contrast agents, and the methods for manufacture and therapeutic use thereof.